Major depressive disorder is a mental disorder characterized by a pervasive low mood, low self-esteem, and loss of interest or pleasure in normally enjoyable activities. The term “major depressive disorder” (which is also known as clinical depression, major depression, unipolar depression, or unipolar disorder) was selected by the American Psychiatric Association for this symptom cluster under mood disorders in the 1980 version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) classification, and has become widely used since.
The general term depression is often used to describe the disorder, but as it is also used to describe a depressed mood, more precise terminology is preferred in clinical and research use. Major depression is a disabling condition which adversely affects a person's family, work or school life, sleeping and eating habits, and general health. In the United States, approximately 3.4% of people with major depression commit suicide, and up to 60% of all people who commit suicide have depression or another mood disorder.
Major depressive disorder (MDD) is the most prevalent disabling and costly psychiatric disorder, with a lifetime prevalence of 16-20%. Current diagnoses are based on clinical decisions guided by subjective interview-based assessments. Treatment typically involves use of antidepressant medications which is traditionally based on a ‘hit and miss’ approach. To date, over 20 antidepressant medications have been approved for clinical application by the Food and Drug Administration. However, despite this wide selection of medications, there are a number of pressing problems associated with this treatment approach.
The success rate of treatment is only approximately 50%. The large proportion of non-responding patients requires additional extended and costly treatment as well as switching of antidepressants to treat symptoms that can last several months. The side effects associated with the prescription of higher therapeutic doses of antidepressants along with the prolonged treatment duration usually results in treatment non-adherence and disease relapse. Relapse increases the risk to further recurrences substantially. There are currently no means to predict which patients will benefit the most from the selection of available antidepressants. Common approaches to increase therapeutic efficacy rely on clinical decision making, without the aid of biological parameters, rendering selection of optimal treatment strategies difficult. Ultimately, there are no objective tools to predict or monitor treatment response. There are no means of sub-stratifying patients based on distinct differences in the underlying disease phenotype. Treatment may have differential effects on distinct molecular etiologies and it is essential to determine whether such differences can be identified before treatment initiation. This would reduce the time to remission, prevent recurrence and side effects, and improve the long term outcome.
Therefore, there is an urgent clinical need to identify objective molecular biomarkers which predict antidepressant treatment response. Such an approach would enable identification of responders and non-responders prior to treatment initiation. It would promote a more informed choice of antidepressant medication and reduce unnecessary drug-exposure and side effects for the non-responders. The healthcare system and the clinical development of novel drugs would benefit by cutting costs regarding the large group of non-responders. The current work aims to develop molecular tools that can be used to optimize the prediction and monitoring of responses to antidepressant treatment.